Almqvist E, Andrew S, Theilmann J, Goldberg P, Zeisler J, Drugge U, Grandell U, Tapper-Persson M, Winblad B, Hayden M
Department of Geriatric Medicine, Karolinska Institute, Stockholm, Sweden.
Hum Genet. 1994 Aug;94(2):124-8. doi: 10.1007/BF00202856.
This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG)n, GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.
本研究旨在确定瑞典亨廷顿舞蹈症（HD）潜在突变的起源数量。利用六种不同的多态性标记（(CCG)n、GT70、674、BS1、E2和4.2）为23个不同的HD家族构建单倍型，其中包括该基因内的两个标记。此外，还进行了广泛的系谱调查，并研究了单倍型的地理起源。观察到十种不同的单倍型，这表明瑞典HD突变存在多个起源。对HD基因内的两个多态性标记（CCG重复序列和GT70）的分析表明，瑞典HD突变至少有三个起源。其中一种单倍型（7/A）在家族中占比89%，这表明大多数瑞典HD家族是通过一个古老起源的单一HD突变联系起来的。此外，之前被认为没有亲缘关系的三个家族可以追溯到15世纪的一个共同祖先，这一发现与该假设一致。
